This K24 application provides 33% salary support to Dr. Hauser to allow him to mentor MD or MD/PhD fellows, improve his mentorship skills, and pursue patient-oriented research in the area of hospital-acquired bacterial pathogens. In particular, this award will allow him to continue current research on the role of Pseudomonas aeruginosa type III secretion in the progression of pneumonia. Bacterial type III secretion systems form needle-like structures that inject toxins called effector proteins directly into the cytosol of host cells. The goal of this study is to determine how P. aeruginosa wields effector proteins in vivo to cause severe pneumonia. The focus will be on interactions between the host innate immune system and effector proteins. The relevance of these findings will be confirmed in human patients infected with P. aeruginosa. In addition to expediting current research, this award will allow Dr. Hauser to expand his research into a new area. Approaches used in the past to address the question of why some P. aeruginosa strains are more virulent than others will now be applied to another hospital-acquired pathogen: Acinetobacter baumannii. Accessory genomic elements (genetic material found in some strains but not in others) will be identified that encode pathogenic factors and enhance the virulence of strains containing them. These markers for hypervirulent strains will be validated in human patients with A. baumannii infections. Both these projects further characterize disease mechanism by utilizing studies involving face-to-face contact with patients. They are thus ideal training vehicles for junior clinician investigators. In summary, this K24 award will provide salary support and research funds to allow Dr. Hauser to spend more of his time mentoring clinical fellows in patient-oriented research, to expand his patient-oriented research activities, and to enhance his mentoring skills.